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However, very little is known about the immune response to leptomeningeal metastasis. Here, by establishing an immunocompetent mouse model of breast cancer leptomeningeal metastasis, we found that tumor-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells were generated in deep cervical lymph nodes (dCLNs) and played an important role in controlling leptomeningeal metastasis. Mechanistically, T cells in dCLNs displayed a senescence phenotype and their recruitment was impaired in mice bearing cancer cells that preferentially colonized in leptomeningeal space. Upregulation of p53 suppressed the transcription of VLA-4 in senescent dCLN T cells and consequently inhibited their migration to the leptomeningeal compartment. Clinically, CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells from the cerebrospinal fluid of patients with leptomeningeal metastasis exhibited senescence and VLA-4 downregulation. Collectively, our findings demonstrated that CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell immunosenescence drives leptomeningeal metastasis.\n                  <\/jats:p>","DOI":"10.7554\/elife.83272","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T06:15:17Z","timestamp":1670566517000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.83272","source":"Crossref","is-referenced-by-count":14,"title":["VLA-4 suppression by senescence signals regulates meningeal immunity and leptomeningeal metastasis"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7162-8960","authenticated-orcid":true,"given":"Jiaqian","family":"Li","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0064kty71","id-type":"ROR","asserted-by":"publisher"}],"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial 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